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Older age, lower gait speed, lower gray matter volume, and greater global mean diffusivity of white matter were the best predictors of mortality in patients with cerebral small vessel disease (SVD), in a single-center study.

Results should be viewed with caution because unmeasured variables such as socioeconomic status and genetics or long-term uncontrolled vascular risk factors could have played a role.

Factors that best predicted 8-year mortality in patients 50-85 years of age with cerebral small vessel disease (SVD) included older age, lower gait speed, lower gray matter volume, and a greater global mean diffusivity of white matter, according to a prospective single-center study.

“These factors probably reflect the vital health status of this group,” de Leeuw and colleagues reported online in JAMA Neurology. “Further studies are needed to investigate the reproducibility of our prediction model on mortality.”

They also called for more research to determine whether interventions targeted at SVD or gait impairment would improve patients’ life expectancy.

Mean age of the participants was 65.7 years and 284 (56.5%) were male. A total of 80 participants (15.9%) died during a mean follow-up of 7.8 (1.5) years, reported the investigators. In the final analysis, a total of 494 (98.2%) participants were included and 78 (15.8%) died.

A diffusion tensor imaging sequence was included to assess microstructural integrity of the white matter and all participants underwent a cognitive and motor assessment. Follow-up continued until Nov. 24, 2014, and analysis of all imaging data, carried out with reviewers blinded to clinical information, was performed shortly thereafter.

Mortality was predicted using Cox proportional hazards models with backward stepwise selection and including age, sex, vascular risk factors, gait speed, cognitive index, MRI, and diffusion measures, reported de Leeuw and colleagues. Cognitive index and other conventional SVD markers were not retained in the prediction model.

“Cognitive performance and conventional MRI markers of SVD, including white matter hyperintensities volume, white matter volume, and lacunes, did not significantly contribute to the prediction of mortality, although these factors were associated with 8-year mortality after adjustment for age, sex, and vascular risk factors,” noted the investigators.

While gray matter volume has been associated with mortality, this study showed that it played a significant role in predicting mortality in SVD, said de Leeuw and colleagues. “Because 17 (21.8%) of the patients who died had developed dementia during the follow-up of our study, this may be an explanation for the observed association between lower GM volume at baseline and mortality,” they said. The causes of increased mortality in patients with dementia are not fully understood, the investigators noted.

Nevertheless, two of the study findings are “especially remarkable,” commented Wolf-Dieter Heiss, MD, of the Max Planck Institute for Metabolism Research in Cologne, Germany. “This study is important because precision in prediction of mortality can be improved by imaging modalities, suggesting that these diagnostic procedures should be included in the evaluation of patients with SVD,” he wrote in an accompanying editorial.

First, the study showed that the presence of SVD not only increased risk of vascular death but that it was also significantly related to all-cause mortality. This might be related to pathologic changes in other organ systems caused by SVD, and could be reflected in factors associated with a negative outcome such as gait speed.

Secondly, the integrity of the white matter in this patient population seemed to have higher predictive values than conventional MRI markers. This may be explained by microstructural changes of the white matter preceding the development of white matter hyperintensities, said Heiss.

de Leeuw and colleagues suggested that their results be “interpreted with caution” since unmeasured variables such as socioeconomic status and genetics or long-term uncontrolled vascular risk factors could have played a role. However, they also noted that while the cohort study was hospital-based, there were no restrictions and all consecutive patients were included.

“We believe that our results can be generalized to patients with SVD referred to a general neurologic clinic,” they wrote.

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